In 1942 Albright and his associates described the features of a new clinical syndrome "pseudohypoparathyroidism." in that they have characteristic constitutional features and they do not respond to exogenous parathyroid extract. We previously found that patients with PHP lack the normal rise in UCAMP excretion seen following PTH administration. This indicated that there is a defective hormone receptor-adenylate cyclase complex in this disorder. We have now shown that red cells from patients with PHP are functionally deficient in a recently isolated protein ("G unit") that serves to couple hormone receptor to the catalytic unit of adenylate cyclase. Our results suggest that reduction in G units is the lesion responsible for hormone resistance in PHP and imply that the defect is not limited to PTH target organs (kidney and bone).